This project will be concerned with characterizing alterations in GABA, dopamine, serotonin and peptide-mediated neurotransmission as a function of chronic treatment with antipsychotic drugs such as clozapine and haloperidol. By measuring changes in enzyme activity, receptor binding, concentration and turnover rate of the neurotransmitters in the basal ganglia, the study will attempt to determine the ways in which the neural circuits are able to adapt to the continuous presence of antipsychotic drugs. The use of selective destruction and lesions of specific pathways will aid in the determination of the neurochemical interactions underlying the time dependent therapeutic and adverse effects of antipsychotic medication.